Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:

Time to engraftment defined as the first 3 consecutive days in which ANC >= 500 in both arms (standard myeloablative CBT with and without off-the-shelf expanded cord blood progenitors) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

The log-rank test will be used. Groups will be compared using Gray's test.

Secondary Outcome Measures:

Death without engraftment [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Groups will be compared using Gray's test and log-rank test.

Duration of initial hospitalization [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Graft failure (primary and secondary) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

Incidence and severity of acute and chronic GVHD [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

Incidence of infectious complications [ Time Frame: Up to 100 days post-transplant ] [ Designated as safety issue: No ]

Toxicities will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

Kinetics of immune system recovery as measured by T and B cell subsets, T cell receptor excision circles (TREC), and T cell receptor (TCR) sequencing [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

The kinetics and durability of hematopoietic reconstitution will be assessed and the relative contribution to engraftment of the expanded cord blood product and the unmanipulated unit(s) will be determined by frequent peripheral blood donor chimerism assays.

Non-relapse mortality (NRM) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Relative contribution to engraftment of the expanded cord blood product and the unmanipulated cord blood unit(s) in early and long-term engraftment, determined by frequent determination of donor chimerism in the peripheral blood [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Groups will be compared using Gray's test.

Time to ANC greater than or equal to 100 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Time to ANC greater than or equal to 500 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Time to engraftment, defined as the first of 2 consecutive days in which ANC is at least 500 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Groups will be compared using Gray's test.

Time to platelet engraftment (20k and 50k) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.

I. Compare the time to neutrophil engraftment (absolute neutrophil count [ANC] >= 500) in patients receiving a standard of care myeloablative cord blood transplant (CBT) augmented with an off-the-shelf pre-expanded and cryopreserved cord blood product to those who do not receive the product.

SECONDARY OBJECTIVES:

I. Provide initial data on clinical and economic benefit, such as time to platelet engraftment, duration of initial hospitalization, day 200 transplant related mortality (TRM), death without engraftment, and incidence of severe infections in the first 100 days post-transplant.

II. The kinetics of immune system recovery will also be evaluated in both arms.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Standard of Care Arm:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 to -6. Patients also undergo total-body irradiation (TBI) twice daily (BID) on days -4 to -1.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or thrice daily (TID) (children) or orally (PO) on days -3 to 100 with taper beginning on day 101. Patients also receive mycophenolate mofetil (MMF) IV TID on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin taper if there is no evidence of GVHD and are well-engrafted from one donor unit.

All patients must be in CR as defined by < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with cellularity >= 15% for age

Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator prior to enrollment

Acute lymphoblastic leukemia

High risk CR1 (for example, but not limited to: t(9;22), t(1;19), t(4;11) or other mixed-lineage leukemia [MLL] rearrangements, hypodiploid); or high risk (HR) as defined by referring institution treatment protocol greater than 1 cycle to obtain CR; CR2 or greater

All patients must be in CR as defined by < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with cellularity >= 15% for age

Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator prior to enrollment

Chronic myelogenous leukemia excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to tyrosine kinase inhibitor therapy

Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate (Int)-2 or high risk (i.e., refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology

Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiation prior to initiation of conditioning; diagnostic lumbar puncture is to be performed per protocol

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01690520